The objective of this study is to elucidate the basic mechanisms involved in the regulation of erythropoiesis and to apply this knowledge to human erythropoietic diseases. Erythropoietin appears to have a primary effect on the cytoplasmic membrane of marrow cells to produce an active marrow cytoplasmic factor (MCF) that stimulates nuclear RNA synthesis. The relationship of the hormone's stimulation of the MCF and RNA synthesis, to its stimulation of cyclic GMP wIll be investigated. The polycythemia produced by the Friend virus (FVP) will also be studied. FVP markedly increases erythropOiesis in mice by a mechanism that does not require erythropoietin. The effect of the virus on RNA, DNA and protein synthesis by the mouse spleen will be studied to determine if its mechanism of action is similar to erythropoietin. Metabolic inhibitors will be employed to determine the primary effect of FVP. Ex-hypoxic polycythemic mice will be infected with FVP and Friend virus infected spleen cells will then be studied in vitro. An attempt will be made to infect erythroid cells with the virus in vitro and study the effect of hemoglobin synthesis. The methods developed in these investigations will be applied to the study of polycythemia vera. The amount of MCF in polycythemia vera marrows will be measured and compared to the amount in secondary polycythemia marrows. It is conceivable that the increased erythropoiesis in this disease is due to an abnormal control of the MCF. BIBLIOGRAPHIC REFERENCES: Hankins, W.D. and Krantz, S.B.: In vitro expression of Erythroid Differentiation induced by Friend polycythemia virus. Nature 253: 731-732, 1975. Zaentz, S.D., Krantz, S.B. and Sears, D.A.: Pure Red Cell Aplasia (PRCA): Presence of Proerythroblasts and Response to Splenectomy. (abstract). Clinical Research 23:49a, 1975.